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Follow up data from KEYNOTE-799 demonstrated a high overall response rate with no new safety signals for patients with unresectable, locally advanced, stage III non-small cell lung cancer.
The combination of pembrolizumab (Keytruda) plus concurrent chemoradiation therapy (cCRT) showed antitumor activity in patients with unresectable, locally advanced, stage III non--small cell lung cancer (NSCLC), regardless of PD-L1 status or tumor histology, according to follow up data presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC) Singapore.1
The phase 2 KEYNOTE-799 study (NCT03631784) enrolled a total of 216 patients with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC, with measurable disease per RECIST 1.1. Cohort A consisted of patients with both squamous and nonsquamous NSCLC, while cohort B included patients with nonsquamous NSCLC only.
All patients enrolled in the study received up to 17 cycles of pembrolizumab, administered at a dose of 200 mg, 3 times per week. Patients in cohort A also received physician’s choice of either paclitaxel or carboplatin 3 times per week on cycle 1, and either paclitaxel or carboplatin once weekly with thoracic radiotherapy on cycles 2 and 3.
Patients in cohort B followed the same dosing schedule for pembrolizumab, with the addition of pemetrexed or cisplatin on cycles 1-3 and thoracic radiotherapy during cycle 3.
The dual primary end points of the study were overall response rate (ORR), per RECIST v1.1, and the percentage of patients who developed grade 3 or higher pneumonitis.
A primary analysis of KEYNOTE-799, conducted after 15 weeks or more of follow up was presented during the 2020 ASCO Virtual Scientific Program and simultaneously published in the Journal of Clinical Oncology.2
In this analysis, conducted after an additional 6 months of follow up, the ORR for cohort A (n = 112) was 69.6% (95% CI, 60.2-78.0), with 4 patients (3.6%) showing a complete response (CR). The median duration of response (DOR) for this patient population was not reached, however 82.2% of patients (n = 31) showed a DOR of 12 months or greater.
Response rates in cohort B (n = 61) were similar, with an ORR of 70.5% (95% CI, 57.4-81.5), including 3 patients (4.9%) who achieved a CR. Median DOR was not yet reached, though 72.1% (n = 5) of patients showed a DOR of 12 months or greater.
The median time to response was 2.1 months (range, 1.1-7.6) for cohort A and 2.2 months for cohort B (range, 1.8-10.3)
“Interestingly, in a substantial number of patients who had to discontinue treatment earlier, an ongoing control of the disease or an ongoing response was observed in some patients for a couple of months,” said Martin Reck, MD, PhD, of the Lung Clinic Grosshansdorf in Grosshansdorf, Germany, during an oral presentation of the data.
The 12-month progression-free survival (PFS) rate was 67.7% for cohort A, with a 12-month overall survival (OS) rate of 81.2%. Twelve-month PFS and 12-month OS for cohort B was 65.2% and 88.0%, respectively. Median PFS and median OS was not reached for either cohort.
Overall, 93.8% of patients in cohort A and 95.0% of patients in cohort B reported at least 1 treatment-related adverse event (TRAE). In total, 119 patients reported TRAEs of grades 3-5, with 54 patients discontinuing treatment due to AEs. Five patients experienced TRAEs that led to death.
Moreover, 17 patients experienced grade 3 or higher pneumonitis, though Reck noted that the majority of pneumonitis events were able to be resolved.
“The incidence of treatment-related events was within the established toxicity profiles of chemoradiotherapy and pembolizumab monotherapy,” said Reck.